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ORIGINAL RESEARCH

Effects of Vegetarian Diets on Blood Lipids: A Systematic Review and


Meta-Analysis of Randomized Controlled Trials
Fenglei Wang, MS; Jusheng Zheng, PhD; Bo Yang, MPH; Jiajing Jiang, MS; Yuanqing Fu, PhD; Duo Li, PhD

Background-Vegetarian diets exclude all animal esh and are being widely adopted by an increasing number of people; however,
effects on blood lipid concentrations remain unclear. This meta-analysis aimed to quantitatively assess the overall effects of
vegetarian diets on blood lipids.
Methods and Results-We searched PubMed, Scopus, Embase, ISI Web of Knowledge, and the Cochrane Library through March
2015. Studies were included if they described the effectiveness of vegetarian diets on blood lipids (total cholesterol, low-density
lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride). Weighted mean effect sizes were calculated for net
changes by using a random-effects model. We performed subgroup and univariate meta-regression analyses to explore sources of
heterogeneity. Eleven trials were included in the meta-analysis. Vegetarian diets signicantly lowered blood concentrations of total
cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and nonhigh-density lipoprotein cholesterol,
and the pooled estimated changes were 0.36 mmol/L (95% CI 0.55 to 0.17; P<0.001), 0.34 mmol/L (95% CI 0.57 to
0.11; P<0.001), 0.10 mmol/L (95% CI 0.14 to 0.06; P<0.001), and 0.30 mmol/L (95% CI 0.50 to 0.10; P=0.04),
respectively. Vegetarian diets did not signicantly affect blood triglyceride concentrations, with a pooled estimated mean
difference of 0.04 mmol/L (95% CI 0.05 to 0.13; P=0.40).
Conclusions-This systematic review and meta-analysis provides evidence that vegetarian diets effectively lower blood
concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and nonhigh-density
lipoprotein cholesterol. Such diets could be a useful nonpharmaceutical means of managing dyslipidemia, especially
hypercholesterolemia. ( J Am Heart Assoc. 2015;4:e002408 doi: 10.1161/JAHA.115.002408)
Key Words: cholesterol diet lipoprotein lipids triglyceride vegetarian

yslipidemia is a primary risk factor for the development


of cardiovascular diseases, such as heart disease,
stroke, and coronary artery disease.1,2 Cardiovascular diseases and associated mortality are strongly related to
elevated blood concentrations of total cholesterol (TC), lowdensity lipoprotein cholesterol (LDL-C), and triglyceride
(TG).3,4 Although lipid-lowering drugs like statins and brates
are effective in reducing TC, LDL-C, and TG concentrations,57

From the Department of Food Science and Nutrition, Zhejiang University,


Hangzhou, China.
Accompanying Table S1 and Figures S1 through S5 are available at
http://jaha.ahajournals.org/content/4/10/e002408/suppl/DC1
Correspondence to: Duo Li, PhD, Department of Food Science and Nutrition,
Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China. E-mail:
duoli@zju.edu.cn
Received July 24, 2015; accepted September 9, 2015.
2015 The Authors. Published on behalf of the American Heart Association,
Inc., by Wiley Blackwell. This is an open access article under the terms of the
Creative Commons Attribution-NonCommercial License, which permits use,
distribution and reproduction in any medium, provided the original work is
properly cited and is not used for commercial purposes.

DOI: 10.1161/JAHA.115.002408

major health organizations have maintained that modication


of dietary and lifestyle patterns is the essential approach to
prevention and management of dyslipidemia and cardiovascular diseases.8,9
In recent years, adopting a vegetarian diet has become
increasingly popular. Vegetarian diets exclude all animal esh.
Varieties of vegetarianism include vegan, raw vegan, ovovegetarian, lactovegetarian, lacto-ovovegetarian, and pescovegetarian. Each type of vegetarianism excludes or includes
certain foods.10 Compared with an omnivorous diet, a
vegetarian diet is rich in ber, magnesium, Fe3+, folic acid,
vitamins C and E, omega-6 polyunsaturated fatty acids,
phytochemicals, and antioxidants but low in cholesterol; total
fat and saturated fatty acids; sodium; Fe2+; zinc, vitamins A,
B12, and D11; and especially omega-3 polyunsaturated fatty
acids. A recent meta-analysis of 7 clinical trials and 32
observational studies showed that consumption of vegetarian
diets was associated with lower blood pressure.12 An earlier
meta-analysis of 7 prospective studies that included 124 706
participants reported 29% lower mortality from ischemic heart
disease (relative risk 0.71, 95% CI 0.56 to 0.87), 16% lower
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Vegetarian Diets and Blood Lipids

Wang et al

ovovegetarian, omitting all animal products but eggs; lactovegetarian, omitting all animal products but dairy products;
or lacto-ovovegetarian, omitting all animal products but
including eggs and dairy products. Comparators comprised
an omnivorous diet (control diet) containing meats and dairy
products and plant-derived foods. Outcomes were baseline
and end point values for blood lipids (TC, LDL-C, HDL-C, or TG)
or their difference and the SD or SEM or 95% CI of each
group. Study design comprised RCTs of either parallel or
crossover design.

Study Selection
The title and abstract of each study identied in the search
was screened to determine the studys eligibility for full
review. The full-text report was retrieved if the study
investigated or potentially investigated the effects of vegetarian diets on blood lipid concentrations. Studies that
compared vegan and ovo-, lacto-, or lacto-ovovegetarian diets
and studies that were cross-sectional, cohort, casecontrol,
animal test, nonoriginal research (reviews, editorials, or
commentaries), unpublished, or duplicated were excluded.
Only human studies published in English were included.

Methods
This systematic review and meta-analysis followed the
recommendations of the Preferred Reporting Items for
Systematic Reviews and Meta-Analysis (PRISMA) statement.20

Literature Search
Relevant articles were identied by searching PubMed,
Scopus, Embase, ISI Web of Knowledge, and the Cochrane
Library databases from their starting dates through March
2015. The structured search strategies used the following
format of keywords: (vegetarian diet OR vegan diet OR
vegetarianism OR vegetarian) AND (blood lipids OR total
cholesterol OR low density lipoprotein cholesterol OR high
density lipoprotein cholesterol OR cholesterol OR triglyceride
OR triacylglycerol). Reference lists of original studies or
reviews were also checked for additional publications.
Because the present study is a systematic review and metaanalysis, institutional review board approval was not required
for this project.

Eligibility Criteria
Studies that met the PICOS criteria (participants, interventions, comparators, outcomes, study design) were included.
Participants were studies conducted in adult humans aged
18 years. Interventions comprised a vegetarian diet (intervention diet) including vegan, omitting all animal products;
DOI: 10.1161/JAHA.115.002408

Data Extraction and Risk-of-Bias Assessment


Data extraction was conducted independently by 2 researchers, and any discrepancies were resolved by discussion. Study
characteristics were extracted including author, publication
year, country, study design, sample size, population information (sex, age, body mass index [BMI; calculated as weight in
kilograms divided by height in square meters], health status,
and lipid-lowering medication use), dietary data (type of diet
and duration of consumption), and outcome analysis. In each
trial, the mean and SD of blood lipid concentrations at
baseline and end point in both intervention and control groups
were extracted. For studies that had multiple time points for
the same participants, only the last end point was used for
analysis. In crossover studies, it was recommended to extract
paired t test data that evaluated the value of measurement
on intervention minus measurement on control separately
for each participant21; however, because these data were
rarely provided, we resorted to using mean and SD separately
for intervention and control. This step provided a conservative
estimate of effect and reduced the power of crossover studies
to show real effects of intervention.22 If SDs were not
reported directly, we calculated them from SEM or 95% CI.
Change-from-baseline SD was also estimated using the
equation listed in the Cochrane Handbook.21 Extracted data
were converted to international units. For TC, LDL-C, and
HDL-C, 1 mg/dL was converted to 0.0259 mmol/L; for TG,
1 mg/dL was converted to 0.0113 mmol/L.
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ORIGINAL RESEARCH

mortality from circulatory diseases (relative risk 0.84, 95% CI


0.54 to 1.14), and 12% lower mortality from cerebrovascular
disease (relative risk 0.88, 95% CI 0.70 to 1.06) with
vegetarian diets.13
Regarding the effects of vegetarian diets on blood lipid
concentrations, several cross-sectional studies showed that
vegetarians have signicantly lower concentrations of TC,
LDL-C, and TG compared with omnivores.14,15 Nevertheless,
data from randomized controlled trials (RCTs) evaluating the
effects of vegetarian diets on blood lipid concentrations have
generated mixed ndings, especially regarding high-density
lipoprotein cholesterol (HDL-C) and TG. Some trials16,17 have
indicated that vegetarian diets could lower HDL-C and
increase TG concentrations compared with omnivorous diets;
however, no such effects were observed in other trials.18,19 To
the best of our knowledge, these results have not been
systematically evaluated; therefore, we conducted a metaanalysis of the published RCTs to comprehensively assess the
overall effects of vegetarian diets on blood lipids (TC, LDL-C,
HDL-C, and TG). The aim of the present study was to ascertain
the extent to which a vegetarian diet alters blood lipids.

Vegetarian Diets and Blood Lipids

Wang et al

Data Synthesis and Statistical Analysis

Screening

Identification

A random-effects model described by DerSimonian and Laird


was used because it takes into account both within- and
between-study variability.23 Heterogeneity between studies
was assessed by the Cochrane Q test and I2 statistic. An I2
value of 25%, 50%, and 75% represented low, moderate,
and high degrees of heterogeneity, respectively. To
explore sources of heterogeneity, subgroup and univariate

metaregression analyses were carried out focused on


population information: continent (Oceania, Europe, or North
America), age (<50 or 50 years), BMI (18.5 to 25, 25 to
30, or 30), health status (healthy or with high cardiovascular disease risk and lipid-lowering medication use [some
or none]), intervention type (lactovegetarian, lacto-ovovegetarian, or vegan) and duration (<3 or 3 months), study
design (parallel or crossover), outcome analysis (per protocol or intention to treat), and publication year (before 2000
or 2000 or later). To determine whether any single trial
exerted undue inuence on the overall results, sensitivity
analysis was conducted in which each study was removed
and the effect size recalculated. Furthermore, publication
bias was assessed using Beggs rank correlation test and
Eggers linear regression test. All statistical analyses were
performed using Stata/SE 12.0 for windows (StataCorp).
Except as otherwise specied, P<0.05 was considered
signicant.

Records identified through database


searching (n=2942)
PubMed (n=558)
Scopus (n=811)
Embase (n=717)
ISI Web of Knowledge (n=783)
Cochrane Library (n=73)

Records after duplicates removed


(n=1148)

Eligibility

Records screened
(n=1148)

Included

Additional records identified


through other sources (n=2)
Reference lists (n=2)

Full-text articles assessed


for eligibility
(n=53)

Studies included in
qualitative synthesis
(n=11)

Records excluded (n=1095)


No relevant outcomes or
observational studies
Full-text articles excluded,
with reasons (n=42)
Reviews (n=7)
Not related (n=8)
Articles from the same study (n=7)
Without control group (n=6)
Not randomized (n=3)
Not in English (n=3)
Replies to comments (n=2)
Other reasons (n=6)

Studies included in
quantitative synthesis
(n=11)

Figure 1. Flow diagram of selection of relevant articles.


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ORIGINAL RESEARCH

Risk of bias across studies was assessed using the


Cochrane Collaborations risk of bias tool,21 which rates 7
domains (random sequence generation, allocation concealment, blinding of participants and personnel, blinding of
outcome assessment, incomplete outcome data, selective
reporting and other threats to validity [eg, contamination of
intervention and carryover effect in crossover trials]) as
having low, high, or unclear risk of bias.

Vegetarian Diets and Blood Lipids

Wang et al

Study Characteristics

Results of the Study Selection

Characteristics of the 11 selected studies are shown in


Tables 1 and 2. Six studies were conducted in North America
(all in the United States16,17,19,24,27,28), 4 were conducted in
Europe (2 in Finland18,26 and 1 each in Sweden29 and the
Czech Republic30), and 1 was conducted in Oceania
(Australia25). The sample sizes ranged from 11 to 291, with
a total of 832 participants. One study involved men only,25 1
study involved women only,16 and the other 9 studies
included both men and women. Mean BMI of participants
varied from 24.0 to 35.0, and mean age at baseline ranged
from 28.0 to 56.2 years. Five trials were performed in
participants with higher cardiovascular risk factors such as
overweight17,28 or type 2 diabetes.19,27,30 Several participants in 3 studies used lipid-lowering medication.19,27,30
Among these 11 studies, 7 included a vegan diet,1619,26,27,29

Detailed processes of study selection are shown in


Figure 1. Our search strategy retrieved 2944 unique
citations: 558 from PubMed, 811 from Scopus, 717 from
Embase, 783 from ISI Web of Knowledge, 73 from the
Cochrane Library, and 2 from hand searching the reference
lists. Of these, 2891 citations were excluded after screening titles and abstracts, leaving 53 articles for full-text
review. After reviewing full text, 42 articles were excluded
because they did not meet the study inclusion criteria (eg,
studies without randomization, studies with nonrelated
outcomes, articles from the same study, reviews, replies
to comments). Ultimately, 11 studies were included in
quantitative synthesis.1619,2430

Table 1. Characteristics of Studies Included in the Meta-Analysis: Participants, Interventions, and Comparators
Mean
Age,
Year

Healthy Status

Lipid-Lowering
Medication (E/C)

Intervention

Control*

Study

Country

No. (F/M)

Mean BMI,
kg/m2

Cooper
et al,
198224

US

15 (5/10)

NR

28.0

Healthy subjects

None

Lactovegetarian

Omnivorous

Kestin et al,
198925

Australia

26 (0/26)

25.5

44.0

NR

None

Lactoovovegetarian

Omnivorous

Ling et al,
199226

Finland

18 (14/4)

26.6

42.8

Healthy participants and


patients for unrelated
conditions

NR

Vegan

Omnivorous

Nicholson
et al,
199927

US

11 (5/6)

NR

54.3

With NIDDM

4 (3/1)

Vegan

Omnivorous

Barnard
et al,
200016

US

35 (35/0)

25.5

36.1

Healthy premenopausal women

None

Vegan

Omnivorous

Agren et al,
200118

Finland

29 (28/1)

24.3

50.8

With rheumatoid arthritis

None

Vegan

Omnivorous

Burke et al,
200728

US

176 (153/23)

34.0

44.0

Overweight and obese adults

None

Lactoovovegetarian

Omnivorous

Elkan et al,
200829

Sweden

58 (52/6)

24.0

50.3

With rheumatoid arthritis

None

Vegan

Omnivorous

Barnard
et al,
200919

US

99 (60/39)

34.9

55.6

With type 2 diabetes

54 (27/27)

Vegan

Omnivorous

Kahleova
et al,
201130

Czech

74 (39/35)

35.0

56.2

With type 2 diabetes

38 (22/16)

Lactovegetarian

Omnivorous

Mishra
et al,
201317

US

291 (241/50)

35.0

45.2

With BMI 25 and/or a previous


diagnosis of type 2 diabetes

NR

Vegan

Omnivorous

BMI indicates body mass index; E/C, experiment diet group/control diet group; F, female; M, male; NR, not reported.
*All control diets adopted in these studies were dened as an omnivorous diet because they contained meat and dairy products and plant-derived foods.

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ORIGINAL RESEARCH

Results

Vegetarian Diets and Blood Lipids

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ORIGINAL RESEARCH

Table 2. Characteristics of Studies Included in the Meta-Analysis: Outcomes and Study Design
Baseline TC, mmol/L
(E/C)

Baseline LDL-C, mmol/L


(E/C)

Baseline HDL-C, mmol/L


(E/C)

Baseline TG, mmol/L


(E/C)

Duration

Outcome
Analysis

Design

Cooper et al,
198224

4.1

0.7

3 weeks

PP

CO

Kestin et al,
198925

6.1

4.1

1.5

1.3

6 weeks

PP

CO

Ling et al, 199226

(5.6/5.5)

(3.7/3.6)

(1.3/1.3)

(1.3/1.0)

4 weeks

PP

PL

Nicholson et al,
199927

(5.3/5.6)

(1.2/1.1)

(2.1/2.3)

12 weeks

PP

PL

Barnard et al,
200016

4.2

2.5

1.3

0.9

2 months

PP

CO

Agren et al,
200118

(4.6/5.2)

(3.0/3.5)

(1.2/1.2)

(1.0/1.0)

3 months

PP

PL

Burke et al,
200728

(5.3/5.3)

(1.5/1.5)

18 months

ITT

PL

Elkan et al, 200829

(1.4/1.3)

(1.1/1.1)

12 months

PP

PL

Barnard et al,
200919

(4.8/5.2)

(2.7/3.0)

(1.4/1.3)

(1.7/1.8)

74 weeks

ITT

PL

Kahleova et al,
201130

(4.4/4.2)

(2.5/2.6)

(1.1/1.1)

(2.1/2.1)

12 weeks

ITT

PL

Mishra et al,
201317

(4.8/4.9)

(2.8/2.8)

(1.4/1.5)

(1.4/1.4)

18 weeks

ITT

PL

Study

CO indicates crossover; E/C, experiment diet group/control diet group; HDL-C, high-density lipoprotein cholesterol; ITT, intention to treat; LDL-C, low-density lipoprotein cholesterol; PL,
parallel; PP, per protocol; TC, total cholesterol; TG, triglyceride.

2 included a lacto-ovovegetarian diet,25,28 and 2 included a


lactovegetarian diet.24,30 The average duration of intervention
was 24 weeks (ranging from 3 weeks to 18 months). Five
trials lasted >3 months,1719,28,29 whereas 2 trials lasted
<1 month,24,26 and the remaining trials fell in between.
Seven studies adopted per-protocol analysis,16,18,2427,29 and
4 used intention-to-treat analysis.17,19,28,30 Eight trials used a
parallel design,1719,2630 and the other 3 trials used a
crossover design.16,24,25

Risk of Bias
All studies stated that participants were randomly assigned,
but only 5 studies specied the randomization process, such
as using a computer-generated random number list,16 a
random number table,17,19 or a minimization procedure.28,29
None of the 11 studies mentioned allocation concealment,
and none of the participants in any of the trials were blinded.
Blinding of outcome assessment was not mentioned in any of
the studies. Only 4 studies were analyzed on an intention-totreat basis.17,19,28,30 In 3 studies, not all of the concentrations
listed in the methods were reported.24,27,28 Carryover effect
in the 3 crossover trials may introduce bias, although this was
not mentioned16,24,25 (Table S1).

DOI: 10.1161/JAHA.115.002408

Effects of Vegetarian Diets on Blood Lipid


Concentrations
A total of 10 studies reported data on TC concentrations.
Vegetarian diets signicantly affect TC concentrations, and
the pooled estimated change in TC concentrations was
0.36 mmol/L (95% CI
0.55 to
0.17; P<0.001)
(Figure 2). Moderate to high heterogeneity was detected
(I2=53.5%). Seven studies reported data on LDL-C concentrations. Vegetarian diets caused signicant reduction in LDL-C
concentrations, and the pooled estimated effect was
0.34 mmol/L (95% CI 0.57 to 0.11; P<0.001) (Figure 2). High heterogeneity was found (I2=72.4%). Nine studies
reported results on HDL-C concentrations. Vegetarian diets
also lowered HDL-C concentrations, and the pooled estimated
mean difference was 0.10 mmol/L (95% CI 0.14 to
0.06; P<0.001) (Figure 3). No heterogeneity was shown for
HDL-C (I2=0%). The mean change in TG concentrations was
calculated in 11 trials. Vegetarian diets did not cause a
signicant change in TG concentration, and the pooled
estimated effect was 0.04 mmol/L (95% CI 0.05 to 0.13;
P=0.40) (Figure 3). Low heterogeneity was observed
(I2=19.9%). Because nonHDL-C (the difference between TC
and HDL-C) was also an important target for cardiovascular

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ORIGINAL RESEARCH

Figure 2. Effects of vegetarian diets on (A) TC and (B) LDL-C concentrations. The meta-analysis used the
WMD in the random-effects model. Horizontal lines denote 95% CI. A diamond represents the overall
estimated effect. LDL-C indicates low-density lipoprotein cholesterol; TC, total cholesterol; WMD, weighted
mean difference.

disease risk set by the Canadian Cardiovascular Society in


2012,31 it was calculated from 8 studies, and a meta-analysis
of the effect of vegetarian diets was performed. Vegetarian
diets signicantly decreased nonHDL-C concentrations by
0.30 mmol/L (95% CI 0.50 to 0.10; P=0.04) (Figure 4).
Moderate to high heterogeneity was found (I2=54.8%).
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Subgroup and MetaRegression Analyses


Subgroup analyses showed that the effect of vegetarian
diets on lowering TC concentrations was greater in
participants
with
BMI
ranging
from
18.5
to
25 ( 0.94 mmol/L, 95% CI 1.33 to 0.55) and from
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Figure 3. Effects of vegetarian diets on (A) HDL-C and (B) TG concentrations. The meta-analysis used the
WMD in the random-effects model. Horizontal lines denote 95% CI. A diamond represents the overall
estimated effect. HDL-C indicates high-density lipoprotein cholesterol; TG, triglyceride; WMD, weighted
mean difference.

25 to 30 ( 0.58 mmol/L, 95% CI 0.89 to 0.27) rather


than those >30 ( 0.16 mmol/L, 95% CI 0.30, 0.01)
(Table 3). A greater lowering effect on TC concentrations
was observed in trials analyzed on a per-protocol basis
( 0.64 mmol/L, 95% CI 0.85 to 0.43) compared with
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an intention-to-treat basis ( 0.16 mmol/L, 95% CI 0.30


to 0.01) (Table 3). Similarly, a greater reduction in LDL-C
concentrations was observed in trials conducted in participants with BMI ranging from 18.5 to 25 and from 25 to
30 or analyzed on a per-protocol basis (Table 3).
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Figure 4. Effects of vegetarian diets on nonhigh-density lipoprotein cholesterol concentrations. The


meta-analysis used the WMD in the random-effects model. Horizontal lines denote 95% CI. A diamond
represents the overall estimated effect. WMD, weighted mean difference.

Meta-regressions for BMI (meta-regression P=0.01 in TC


analysis and P=0.02 in LDL-C analysis) and outcome
analysis (meta-regression P=0.01 in TC analysis and
P=0.02 in LDL-C analysis) were signicant, suggesting that
these 2 factors may be substantial sources of heterogeneity
present in TC and LDL-C analyses.
Subgroup and metaregression analyses did not show any
statistically signicant differences in the effect of vegetarian
diets on HDL-C and TG concentrations between subgroups
stratied by population information (continent, age, BMI,
health status, and lipid-lowering medication use), intervention
information (type and duration), study design, outcome
analysis, and publication year (Table 4). For nonHDL-C,
subgroup and metaregression analyses indicated that
reduction was greater in trials conducted in participants with
lower BMI or analyzed on a per-protocol analysis, which could
partly explain the heterogeneity, as for TC and LDL-C
(Table 5).

Sensitivity Analysis and Publication Bias


Sensitivity analysis showed that the pooled estimate of the
effects of vegetarian diets on TC, LDL-C, HDL-C, TG, and non
HDL-C concentrations did not vary substantially with the
exclusion of any 1 study (Figures S1 through S5). Results from
Beggs rank correlation test and Eggers linear regression test
suggested that no obvious publication bias was detected in
the meta-analysis of TC, LDL-C, HDL-C, TG, or nonHDL-C
(Table 6).
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Discussion
The objective of the present study was to examine the effects
of vegetarian diets on blood lipid concentrations. This metaanalysis of 11 RCTs suggests that vegetarian diets had a
signicant lowering effect on the concentrations of blood TC,
LDL-C, HDL-C, and nonHDL-C; however, no remarkable
effect was detected on TG concentrations.
Although a large number of cross-sectional studies14,15
have shown that concentrations of TC, LDL-C, and TG were
much lower in vegetarians than in omnivores, a few
studies32,33 have found no such relationships with HDL-C
and TG concentrations. A meta-analysis of 12 observational
studies with a total of 4177 participants revealed no evidence
showing that HDL-C concentrations differed in vegetarians
and omnivores.34 Another meta-analysis of 12 observational
studies with 1300 participants indicated that vegetarian diets
were effective in lowering TG concentrations.35 Although this
phenomenon was obvious in developing countries, it was
nonsignicant in developed countries. Likewise, results from
RCTs in humans were not necessarily consistent, particularly
those results on HDL-C and TG. Our meta-analysis was
performed based on this inconsistent evidence to assess the
overall effect of vegetarian diets on blood lipid concentrations.
Subgroup and metaregression analyses indicated that the
lowering effects of vegetarian diets on TC, LDL-C, and non
HDL-C concentrations were less evident in obese participants
(BMI 30). Obesity is associated with an increased rate of
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Table 3. Subgroup and Meta-Regression Analyses for TC and LDL-C Concentrations


TC
No. of
Trials

Subgroup Factors

LDL-C
Pooled Effect
(95% CI) mmol/L

I2 (%)

P Value*

P Value

No. of
Trials

Pooled Effect
(95% CI) mmol/L

I2 (%)

P Value*

10

0.36 ( 0.55 to

0.17)

53.5

0.02

0.34 ( 0.57 to

0.11)

72.4

<0.001

10

0.32 ( 0.43 to

0.20)

53.5

0.02

0.30 ( 0.41 to

0.19)

72.4

<0.001

Oceania

0.61 ( 1.14 to

0.08)

0.61 ( 1.11 to

0.11)

Europe

0.58 ( 1.20 to 0.04)

79.8

0.01

0.46 ( 1.04 to 0.11)

87.9

<0.001

North America

0.25 ( 0.40 to

13.0

0.33

0.20 ( 0.35 to

0.0

0.72

Overall analyses
Overall analyses

Continent

0.24

0.09)

Age, y

0.39

0.05)

0.96

<50

0.33 ( 0.53 to

50

0.37 ( 0.80 to 0.05)

0.13)

35.1

0.17

73.5

0.01

BMI, kg/m2

0.79
4

0.30 ( 0.48 to

0.11)

0.30 ( 0.78 to 0.18)

15.1

0.32

88.8

<0.001

0.01

0.01

18.5 to 25

0.94 ( 1.33 to

0.55)

0.74 ( 0.68 to

0.16)

25 to 30

0.58 ( 0.89 to

0.27)

0.92

0.42 ( 0.68 to

0.16)

0.46

30

0.16 ( 0.30 to

0.01)

0.85

0.13 ( 0.27 to 0.01)

0.62

Health status

0.08

Healthy

0.53 ( 0.82 to

0.23)

0.92

High CVD risk

0.15 ( 0.30 to

0.01)

0.93

Lipid-lowering
medication

0.44
1

0.30 ( 0.62 to 0.02)

0.13 ( 0.27 to 0.01)

0.0

0.62

0.20

0.19

Some

0.17 ( 0.39 to 0.06)

0.95

0.06 ( 0.26 to 0.14)

0.79

None

0.51 ( 0.84 to

70.9

0.01

0.40 ( 0.68 to

4.6

0.31

0.18)

Intervention

0.11)

0.59

0.23

0.30 ( 0.63 to 0.02)

39.6

0.20

0.04 ( 0.28 to 0.20)

0.28 ( 0.83 to 0.27)

70.1

0.07

0.61 ( 1.11 to

0.11)

0.44 ( 0.73 to

0.14)

60.1

0.03

0.37 ( 0.65 to

0.09)

73.3

0.01

<3

0.38 ( 0.57 to

0.19)

0.46

0.30 ( 0.59 to

0.01)

50.2

0.11

0.33 ( 0.67 to 0.02)

78.5

0.003

0.35 ( 075 to 0.05)

85.9

0.001

Crossover

0.55 ( 0.80 to

0.29)

0.96

0.40 ( 0.68 to

0.11)

4.6

0.31

Parallel

0.29 ( 0.53 to

0.05)

60.8

0.02

0.31 ( 0.61 to

0.01)

80.1

<0.001

PP

0.64 ( 0.85 to

0.43)

0.50

0.57 ( 0.82 to

0.33)

35.3

0.20

ITT

0.16 ( 0.30 to

0.01)

0.85

0.13 ( 0.27 to 0.01)

0.62

Lactovegetarian
Lactoovovegetarian
Vegan
Duration, months

0.64

Design

0.92

0.26

Analysis

0.68

0.01

Publication year

P Value

0.02

0.45

0.29

Before 2000

0.52 ( 0.83 to

0.21)

0.74

0.64 ( 1.08 to

0.20)

0.80

2000 or later

0.32 ( 0.56 to

0.09)

69.0

0.01

0.28 ( 0.54 to

0.02)

79.1

<0.001

BMI indicates body mass index; CVD, cardiovascular disease; ITT, intention to treat; LDL-C, low-density lipoprotein cholesterol; PP, per protocol; TC, total cholesterol.
*P for heterogeneity

P for metaregression analysis.

Results from xed-effect analysis.

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Table 4. Subgroup and MetaRegression Analyses for HDL-C and TG Concentrations


HDL-C
No. of
Trials

Subgroup Factors

Overall analyses

TG
Pooled Effect
(95% CI) mmol/L

I2 (%)

P Value*

P Value

No. of
Trials

Pooled Effect
(95% CI) mmol/L

I2 (%)

P Value*

0.10 ( 0.14 to

0.06)

0.58

11

0.04 ( 0.05 to 0.13)

19.9

0.25

0.10 ( 0.14 to

0.06)

0.58

11

0.05 ( 0.03 to 0.13)

19.9

0.25

Oceania

0.09 ( 0.25 to 0.07)

Europe

0.11 ( 0.17 to

0.05)

0.45

0.12 ( 0.27 to 0.04)

0.67

North America

0.09 ( 0.18 to

0.01)

21.0

0.28

0.08 ( 0.01 to 0.18)

0.68

Overall analyses

Continent

0.72

Age, y

0.09
0.26 (0.01 to 0.51)

0.97

<50

0.10 ( 0.17 to

0.03)

0.57

50

0.10 ( 0.16 to

0.03)

12.1

0.34

BMI, kg/m2

0.08
6

0.09 ( 0.03 to 0.20)

35.4

0.17

0.09 ( 0.26 to 0.07)

0.92

0.82

0.72

18.5 to 25

0.08 ( 0.24 to 0.07)

57.9

0.12

0.06 ( 0.26 to 0.13)

0.58

25 to 30

0.14 ( 0.24 to

0.04)

0.58

0.08 ( 0.20 to 0.36)

68.1

0.04

30

0.09 ( 0.14 to

0.03)

1.6

0.36

0.06 ( 0.07 to 0.18)

2.6

0.38

Health status

0.29

Healthy

0.20 ( 0.36 to

0.04)

High CVD risk

0.09 ( 0.15 to

0.04)

0.49

Lipid-lowering
medication

0.33
2

0.08 ( 0.10 to 0.27)

33.0

0.22

0.06 ( 0.06 to 0.18)

0.54

0.99

Some

0.10 ( 0.18 to

None

0.10 ( 0.21 to 0.02)

0.03)

0.20

5.6

0.35

0.16 ( 0.46 to 0.14)

0.85

38.9

0.20

0.07 ( 0.04 to 0.17)

15.0

0.32

Intervention

0.76

0.85

0.04 ( 0.22 to 0.13)

0.53

0.09 ( 0.25 to 0.07)

0.15 ( 0.04 to 0.35)

28.2

0.24

0.09 ( 0.15 to

0.03)

2.8

0.40

0.02 ( 0.12 to 0.15)

27.2

0.22

<3

0.13 ( 0.19 to

0.07)

0.86

0.04 ( 0.13 to 0.21)

43.7

0.11

0.07 ( 0.13 to 0.00)

9.6

0.34

0.04 ( 0.07 to 0.15)

0.47

Parallel

0.09 ( 0.14 to

0.04)

0.57

0.00 ( 0.10 to 0.10)

3.0

0.41

Crossover

0.15 ( 0.26 to

0.04)

0.34

0.13 ( 0.03 to 0.29)

32.4

0.23

PP

0.12 ( 0.19 to

0.05)

0.53

0.03 ( 0.10 to 0.17)

35.9

0.15

ITT

0.09 ( 0.14 to

0.03)

1.6

0.36

0.06 ( 0.07 to 0.18)

2.6

0.38

Lactovegetarian
Lactoovovegetarian
Vegan

0.12 ( 0.20 to

0.04)

Duration, months

0.20

Design

0.81

0.39

Analysis

0.17

0.54

Publication year

0.99

0.89

0.98

Before 2000

0.11 ( 0.23 to 0.02)

0.85

0.02 ( 0.24 to 0.27)

53.3

0.09

2000 or later

0.10 ( 0.15 to

19.7

0.28

0.05 ( 0.04 to 0.15)

0.7

0.42

0.04)

P Value

BMI indicates body mass index; CVD, cardiovascular disease; HDL-C, high-density lipoprotein cholesterol; ITT, intention to treat; PP, per protocol; TG, triglyceride.
*P for heterogeneity.

P for metaregression analysis.

Results from xed-effect analysis.

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Table 5. Subgroup and MetaRegression Analyses for NonHDL-C Concentrations


Non-HDL-C
Subgroup Factors

No. of Trials

Overall analyses
Overall analyses

Pooled Effect (95% CI) mmol/L

I2 (%)

P Value*

0.30 ( 0.50 to

0.10)

54.8

0.03

0.25 ( 0.37 to

0.13)

54.8

0.03

Continent

0.35

0.46 ( 1.05 to 0.14)

82.4

0.003

0.18 ( 0.33 to

0.68

Oceania

0.52 ( 0.99 to

Europe

North America

0.05)

0.03)

Age, y

0.83

<50

0.26 ( 0.44 to

50

0.27 ( 0.66 to 0.12)

0.08)

9.8

0.34

75.3

0.01

BMI, kg/m2
18.5 to 25

P Value

0.01
1

0.78 ( 1.13 to

0.43)
0.15)

25 to 30

0.42 ( 0.69 to

30

0.12 ( 0.26 to 0.02)

0.74

0.79

Health status

0.32

Healthy

0.34 ( 0.69 to 0.01)

High CVD risk

0.11 ( 0.26 to 0.03)

0.84

Lipid-lowering medication

0.08

Some

0.09 ( 0.29 to 0.11)

0.69

None

0.55 ( 0.83 to

35.5

0.21

0.28)

Intervention

0.47

Lactovegetarian

0.05 ( 0.31 to 0.21)

Lacto-ovovegetarian

0.52 ( 0.99 to

0.05)

Vegan

0.33 ( 0.58 to

0.08)

57.4

0.04

Duration, months

0.72

<3

0.24 ( 0.47 to

0.35 ( 0.74 to 0.03)

0.01)

21.4

0.28

80.3

0.01

Design

0.56

Crossover

0.40 ( 0.68 to

0.12)

0.55

Parallel

0.26 ( 0.52 to

0.01)

63.6

0.02

Analysis

0.02

PP

0.51 ( 0.77 to

0.25)

ITT

0.12 ( 0.26 to 0.02)

25.7

0.25

0.79

Publication year

0.70

Before 2000

0.42 ( 0.81 to

0.03)

0.38

2000 or later

0.28 ( 0.51 to

0.05)

68.5

0.01

BMI indicates body mass index; CVD, cardiovascular disease; HDL-C, high-density lipoprotein cholesterol; ITT, intention to treat; PP, per protocol.
*P for heterogeneity.

P for metaregression analysis.

Results from xed-effect analysis.

cholesterol synthesis.36 Leptin, a hormone secreted by


adipocytes, could promote hepatic cholesterol clearance37;
however, most obese subjects always experience leptin
DOI: 10.1161/JAHA.115.002408

resistance, and its effects might be diminished or lacking in


the obese state.38 Consequently, the lowering effect of
vegetarian diets on TC, LDL-C, and nonHDL-C concentrations
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Vegetarian Diets and Blood Lipids

Wang et al

No. of
Trials

P for
Beggs
Test

Pooled Effect
(95% CI) mmol/L

P for
Eggers
Test

TC

10

0.36 ( 0.55 to

0.17)

0.28

0.27

LDL-C

0.34 ( 0.57 to

0.11)

0.37

0.54

HDL-C

0.10 ( 0.14 to

0.06)

1.00

0.93

TG

11

0.04 ( 0.05 to 0.13)

0.35

0.16

NonHDLC

0.30 ( 0.50 to

0.27

0.42

0.10)

HDL-C indicates high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein


cholesterol; TC, total cholesterol; TG, triglyceride.

could be attenuated in obese participants. Subgroup and


meta-regression analyses also showed that reduction in TC,
LDL-C, and nonHDL-C concentrations was greater in trials
that adopted per-protocol analysis compared with those that
adopted intention-to-treat analysis. This result is consistent
with the idea that, on average, per-protocol analysis tends to
provide higher estimates of effect than the intention-to-treat
analysis.39 A per-protocol analysis is performed in which
participants are included only if they received the intended
intervention in line with the protocol, whereas an intention-totreat analysis includes all randomized participants.21 Losses
do not retain the intervention effect, and missing data in
trials will lead to systematic differences between the
approaches.39

Studies have shown that a 1-mmol/L reduction in TC and


LDL-C levels results in a 26.6% to 29.5% decrease for any
cardiovascular diseaserelated event.40 The average reductions of TC and LDL-C concentrations following a vegetarian
diet intervention included in this meta-analysis were 0.36 and
0.34 mmol/L, respectively, which would correspond to a
decrease in cardiovascular disease risk of about 9.0% to
10.6%. Vegetarian diets may reduce blood cholesterol
concentrations through several mechanisms. Vegetarian diets
are low in cholesterol, total fat, and saturated fatty acids,11
leading to less absorption and conversion to blood cholesterol.41 Moreover, vegetarian diets provide a high intake of
dietary ber and many health-promoting phytochemicals
including phytosterols, phenolics, carotenoids, avonoids,
indoles, saponins, and suldes, derived primarily from fruits,
vegetables, whole grains, legumes, nuts, and various soy
products.42 These phytochemicals can exert substantial
inuence on cholesterol levels via multiple mechanisms.
Phytosterols reduce intestinal cholesterol absorption by
competing with cholesterol for a place in the mixed
micelles.43 Phenolics inhibit the oxidation of LDL-C, improving
cardiovascular health.44 Flavonoids and saponins disrupt the
cholesterol micelle solubility, leading to potential reduction in
cholesterol absorption.45 Suldes or organosulfur compounds
decrease blood lipids, especially TC and nonHDL-C, like LDLC, by inhibiting the biosynthesis of cholesterol.46
Like other cholesterol subfractions (eg, nonHDL-C), blood
HDL-C concentrations were also decreased after the vegetarian diet intervention. A reduction in the apolipoprotein A-I

Figure 5. Effects of vegetarian diets on weight loss. The meta-analysis used the WMD in the randomeffects model. Horizontal lines denote 95% CI. A diamond represents the overall estimated effect. WMD,
weighted mean difference.

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ORIGINAL RESEARCH

Table 6. Results of Publication Bias Test

Vegetarian Diets and Blood Lipids

Wang et al

DOI: 10.1161/JAHA.115.002408

signicantly associated with decrease of TC and LDL-C50;


therefore, some of the effect of the change in TC and LDL-C in
this meta-analysis could be a consequence of weight loss.
Fifth, our analysis covers a long time span of 30 years, with
the oldest study performed in 1982 and the latest trial
conducted in 2013. The time of study may be an important
confounder because lifestyles changed and medical sciences
advanced considerably; however, no signicant difference was
found between studies published before 2000 and those
published in and after 2000 in subgroup and univariate meta
regression analyses. Finally, studies that examined the effects
of vegetarian diets on serum lipid concentrations and on
plasma lipid concentrations were both included in this metaanalysis to guarantee a considerable number of participants.
The commonly recommended anticoagulant for plasma is
disodium ethylenediaminetetraacetate. Its use may produce a
shift of water from red blood cells to plasma and thus dilutes
the plasma and lowers the concentration of lipids.51 Comparing nal values may introduced bias due to the difference
between plasma lipids and serum lipids. This meta-analysis
was analyzed based on changes from baseline to minimize
this bias.
In conclusion, vegetarian diets could effectively lower
blood concentrations of TC, LDL-C, HDL-C, and nonHDL-C.
These ndings have important public health implications
with regard to the management of dyslipidemia, especially
hypercholesterolemia, via dietary intervention. Further welldesigned RCTs that are designed to evaluate the effects
of specic vegetarian diets on blood lipids are required,
and additional studies with detailed population information
should be performed to clarify the possible mechanism.

Sources of Funding
This study was funded by the National Basic Research
Program of China (973 Program: 2015CB553604).

Disclosures
None.

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ORIGINAL RESEARCH

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SUPPLEMENTAL MATERIAL

Table S1. Assessment of risk of bias across studies


Figure S1. Sensitivity analysis of 10 studies evaluating blood TC concentrations
Figure S2. Sensitivity analysis of 7 studies evaluating blood LDL-C concentrations
Figure S3. Sensitivity analysis of 9 studies evaluating blood HDL-C concentrations
Figure S4. Sensitivity analysis of 11 studies evaluating blood TG concentrations
Figure S5. Sensitivity analysis of 8 studies evaluating blood non-HDL-C concentrations

Table S1. Assessment of risk of bias across studies

Cooper et al,
1982
Kestin et al,
1989
Ling et al,
1992
Nicholson et al,
1999
Barnard et al,
2000
Agren et al,
2001
Burke et al,
2007
Elkan et al,
2008
Barnard et al,
2009
Kahleova et al,
2011
Mishra et al,
2013

Random
sequence
generation
(selection bias)

Allocation
concealment
(selection bias)

Blinding of
participants and
personnel
(performance bias)

Blinding of
outcome
assessment
(detection bias)

Incomplete
outcome data
(attrition bias)

Selective
reporting
(reporting bias)

Other bias

Unclear risk

Unclear risk

High risk

Unclear risk

High risk

High risk

Unclear risk

Unclear risk

Unclear risk

High risk

Unclear risk

High risk

Low risk

Unclear risk

Unclear risk

Unclear risk

High risk

Unclear risk

High risk

Low risk

Low risk

Unclear risk

Unclear risk

High risk

Unclear risk

High risk

High risk

Low risk

Low risk

Unclear risk

High risk

Unclear risk

High risk

Low risk

Unclear risk

Unclear risk

Unclear risk

High risk

Unclear risk

High risk

Low risk

Low risk

Low risk

Unclear risk

High risk

Unclear risk

Low risk

High risk

Low risk

Low risk

Unclear risk

High risk

Unclear risk

High risk

Low risk

Low risk

Low risk

Unclear risk

High risk

Unclear risk

Low risk

Low risk

Low risk

Unclear risk

Unclear risk

High risk

Unclear risk

Low risk

Low risk

Low risk

Low risk

Unclear risk

High risk

Unclear risk

Low risk

Low risk

Low risk

Figure S1. Sensitivity analysis of 10 studies evaluating blood TC concentrations

Figure S2. Sensitivity analysis of 7 studies evaluating blood LDL-C concentrations

Figure S3. Sensitivity analysis of 9 studies evaluating blood HDL-C concentrations

Figure S4. Sensitivity analysis of 11 studies evaluating blood TG concentrations

Figure S5. Sensitivity analysis of 8 studies evaluating blood non-HDL-C concentrations

Effects of Vegetarian Diets on Blood Lipids: A Systematic Review and MetaAnalysis of


Randomized Controlled Trials
Fenglei Wang, Jusheng Zheng, Bo Yang, Jiajing Jiang, Yuanqing Fu and Duo Li
J Am Heart Assoc. 2015;4:e002408; originally published October 27, 2015;
doi: 10.1161/JAHA.115.002408
The Journal of the American Heart Association is published by the American Heart Association, 7272 Greenville Avenue,
Dallas, TX 75231
Online ISSN: 2047-9980

The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://jaha.ahajournals.org/content/4/10/e002408

Data Supplement (unedited) at:


http://jaha.ahajournals.org/content/suppl/2015/10/27/JAHA.115.002408.DC1.html

Subscriptions, Permissions, and Reprints: The Journal of the American Heart Association is an online only Open
Access publication. Visit the Journal at http://jaha.ahajournals.org for more information.

Downloaded from http://jaha.ahajournals.org/ by guest on July 1, 2016

SUPPLEMENTAL MATERIAL

Table S1. Assessment of risk of bias across studies


Figure S1. Sensitivity analysis of 10 studies evaluating blood TC concentrations
Figure S2. Sensitivity analysis of 7 studies evaluating blood LDL-C concentrations
Figure S3. Sensitivity analysis of 9 studies evaluating blood HDL-C concentrations
Figure S4. Sensitivity analysis of 11 studies evaluating blood TG concentrations
Figure S5. Sensitivity analysis of 8 studies evaluating blood non-HDL-C concentrations

Table S1. Assessment of risk of bias across studies

Cooper et al,
1982
Kestin et al,
1989
Ling et al,
1992
Nicholson et al,
1999
Barnard et al,
2000
Agren et al,
2001
Burke et al,
2007
Elkan et al,
2008
Barnard et al,
2009
Kahleova et al,
2011
Mishra et al,
2013

Random
sequence
generation
(selection bias)

Allocation
concealment
(selection bias)

Blinding of
participants and
personnel
(performance bias)

Blinding of
outcome
assessment
(detection bias)

Incomplete
outcome data
(attrition bias)

Selective
reporting
(reporting bias)

Other bias

Unclear risk

Unclear risk

High risk

Unclear risk

High risk

High risk

Unclear risk

Unclear risk

Unclear risk

High risk

Unclear risk

High risk

Low risk

Unclear risk

Unclear risk

Unclear risk

High risk

Unclear risk

High risk

Low risk

Low risk

Unclear risk

Unclear risk

High risk

Unclear risk

High risk

High risk

Low risk

Low risk

Unclear risk

High risk

Unclear risk

High risk

Low risk

Unclear risk

Unclear risk

Unclear risk

High risk

Unclear risk

High risk

Low risk

Low risk

Low risk

Unclear risk

High risk

Unclear risk

Low risk

High risk

Low risk

Low risk

Unclear risk

High risk

Unclear risk

High risk

Low risk

Low risk

Low risk

Unclear risk

High risk

Unclear risk

Low risk

Low risk

Low risk

Unclear risk

Unclear risk

High risk

Unclear risk

Low risk

Low risk

Low risk

Low risk

Unclear risk

High risk

Unclear risk

Low risk

Low risk

Low risk

Figure S1. Sensitivity analysis of 10 studies evaluating blood TC concentrations

Figure S2. Sensitivity analysis of 7 studies evaluating blood LDL-C concentrations

Figure S3. Sensitivity analysis of 9 studies evaluating blood HDL-C concentrations

Figure S4. Sensitivity analysis of 11 studies evaluating blood TG concentrations

Figure S5. Sensitivity analysis of 8 studies evaluating blood non-HDL-C concentrations

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